AK4
Domain
Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon GTP/ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent GTP/ATP hydrolysis.
Function
Broad-specificity mitochondrial nucleoside phosphate kinase involved in cellular nucleotide homeostasis by catalyzing nucleoside-phosphate interconversions (PubMed:19073142, PubMed:19766732, PubMed:23416111, PubMed:24767988). Similar to other adenylate kinases, preferentially catalyzes the phosphorylation of the nucleoside monophosphate AMP with ATP as phosphate donor to produce ADP (PubMed:19766732). Phosphorylates only AMP when using GTP as phosphate donor (PubMed:19766732). In vitro, can also catalyze the phosphorylation of CMP, dAMP and dCMP and use GTP as an alternate phosphate donor (PubMed:19766732, PubMed:23416111). Moreover, exhibits a diphosphate kinase activity, producing ATP, CTP, GTP, UTP, TTP, dATP, dCTP and dGTP from the corresponding diphosphate substrates with either ATP or GTP as phosphate donors (PubMed:23416111). Plays a role in controlling cellular ATP levels by regulating phosphorylation and activation of the energy sensor protein kinase AMPK (PubMed:24767988, PubMed:26980435). Plays a protective role in the cellular response to oxidative stress (PubMed:19130895, PubMed:23474458, PubMed:26980435).
Sequence Similarities
Belongs to the adenylate kinase family. AK3 subfamily.
Tissue Specificity
Highly expressed in kidney, moderately expressed in heart and liver and weakly expressed in brain.
Cellular localization
- Mitochondrion matrix
Alternative names
AK3, AK3L1, AK4, Adenylate kinase 3-like, GTP:AMP phosphotransferase AK4
Database links
swissprot:P27144 omim:103030 entrezGene:205 entrezGene:100507855